1. Field of the Invention
The present invention is related to ophthalmic treatment. Particularly, it relates to photodynamic therapy methods and formulations for treating choroidal neovasculature (CNV) associated with age-related macular degeneration (AMD).
2. Invention Disclosure Statement
Age-related macular degeneration (AMD) is a progressive retinal disease wherein the light-sensing cells in the central area of vision, the macula, stop working and eventually die. The disease is thought to be caused by a combination of genetic and environmental factors, and it is most common in people age sixty and over. AMD is the leading cause of visual impairment in senior citizens. An estimated fifteen million people in the United States have it, and approximately two million new cases are diagnosed annually.
Two basic forms of AMD are exudative neovascular (wet form) and non-neovascular (dry form). Dry form involves macula thinning and pigmentation disturbance. Dry form progresses more slowly compared to wet form. In wet form, abnormal blood vessels known as choroidal neovascularization (CNV) grow under the retina and macula. These new blood vessels bleed and leak fluid causing macula to bulge, thus impairing central vision. Wet form can manifest in two types: classic neovascularization (seen) and occult neovascularization (hidden).
Untreated AMD is a progressive disease state leading to further vision loss. Wet type deteriorates vision faster. Currently, there is no cure for macular degeneration, but some treatments may delay progression or even improve vision. Vision lost due to AMD is generally irreversible.
Current popular AMD treatment methods include laser photocoagulation, Transpupillary Thermo-Therapy (TTT), anti-angiogenic treatment, and most recently PhotoDynamic Therapy (PDT).
Traditionally, thermal lasers were used to cease blood vessel leaking that caused wet form of AMD. Unfortunately, thermal laser treatment also leaves a permanent blind spot in the patient's field of vision. It can also damage normal retinal structure and is suitable only in selected cases where newly formed vessels are not close to the central macular area.
Transpupillary Thermo-Therapy (TTT) utilizes an infrared laser to heat the abnormal blood vessels. This closes the blood vessel without damaging the normal retinal structure. The treatment is aimed at preserving vision. It often requires more than one treatment and regular follow-up appointments for good results.
U.S. Patent Publication 2006/127481 by Kataoka et al., describes the use of polymer micelles for drug delivery to posterior regions of eye affected by neovascularizations. The shell is formed of hydrophilic polymer chains and the core is hydrophobic polymer chains. Such delivery systems are used in PhotoDynamic Therapy (PDT) for treating AMD. A newer PDT treatment option is with verteporfin (Visudyne™ FDA approved) photosensitizer injected into a vein in the patient's arm. After a specific time gap, a non-thermal laser is radiated into the patient's eyes. The radiation activated photosensitizer destroys abnormal blood vessels. Changes in vision, including blurring, decreased sharpness in vision and gaps in vision are commonly reported side effects. This method has limitations because it may require more than one treatment. Moreover, invasive intravenous verteporfin injection unnecessarily exposes the entire body to the photosensitizer.
U.S. Pat. No. 6,942,655 by Peyman, discloses a combination of methods for treating and preventing progression of AMD characterized by fluid leakage. Here, a laser photocoagulation method is used simultaneously or concomitantly with PDT to treat AMD. In another U.S. Pat. No. 6,840,933 by Pang et al, a method is disclosed for detecting and treating growth of feeder blood vessels to neovasculature in choroidal or sub-retinal layers of eye by photocoagulation with laser radiation.
Miller et. al, in U.S. Pat. No. 7,125,542, discloses a method for treating unwanted choroidal neovasculature by combining PDT with an anti-angiogenesis factor, for example, angiostatin or endostatin, or with an apoptosis-modulating factor.
In U.S. Pat. No. 6,800,086 by Strong, use of a PDT method is disclosed with a reduced fluence rate for treating wet form of AMD. The preferred photosensitizer is green porphyrin formulated in liposome for administration. However, these conventional liposome formulations exhibit a short plasma half life and are quickly taken up by mononuclear phagocytes.
U.S. Pat. No. 7,320,786 by Chen discloses a PDT based treatment method for eye diseases. In this method, a photosensitizing agent is tagged to specifically bind to abnormal endothelium cells of neovascular tissue. The preferred photosensitizer absorbs light in the range of 500 to 1100 nm.
The aforementioned prior art treatment methods require multiple treatments and are expensive. Moreover, thermal laser photocoagulation causes damage to normal surrounding retinal cells leaving a permanent blind spot.
In the present invention most of the drawbacks are minimized or eliminated. An improved PDT method and formulation to treat AMD are provided. It improves and stabilizes deteriorating vision and minimizes fluid leakage.